Search

We read with interest the recent work by Stevens et al 1 showing the association between zonulin, fatty acid binding protein 2 (FABP2) and lipopolysaccharide (LPS) plasma levels and increased gut permeability in asymptomatic gastroenterology patients with depression and anxiety disorders, when compared with controls. Zonulin is a regulator of intestinal permeability and a marker of intestinal barrier impairment,2 which is reported in the irritable bowel syndrome (IBS) and functional dyspepsia (FD),3 both of which are associated with anxiety and depression.4 5 The tight junctional protein zonulin (ZO-1) is significantly reduced in these patients possibly driving a low-grade immune response.3 6 The utility of serum zonulin as a biomarker is controversial. One study observed higher serum zonulin levels in coeliac disease (CD) (mean 0.033 ng/mg total proteins), non-coeliac gluten sensitivity (NCGS) (mean 0.030 ng/mg total proteins) and IBS-diarrhoea (mean 0.012 ng/mg total proteins) patients, versus healthy controls,7 but the Malmo Diet and Cancer cardiovascular cohort showed no association between serum zonulin and reported GI symptoms or IBS and FD.8 We aimed to examine serum zonulin as a biomarker for IBS and FD. Adult participants were recruited from two sources9; (1) a population-based study (n=242; mean age 62.1 (SD=11.9) years; 45.9% female) and (2) a two-site hospital-based study (n=102; mean age 45.0 (SD=16.2) years; 67.4% female). In the population-based study, IBS (n=40) and FD (n=42) were diagnosed according to modified Rome III criteria, while CD (n=6), gluten intolerance (n=6) and NCGS (n=44) had self-reported doctor diagnoses. Healthy controls (n=182) did not meet Rome …

The global population has more than doubled over the past 40 years, supported by the ‘green revolution’ in agriculture producing high-yield grain varieties, including wheat, that are central to the modern diet.1 Wheat covers more than 200 million hectares of land,2 is the third most produced cereal behind rice and maize,3 and is responsible for one-fifth of the world’s calorific input.2 Wheat contains gluten proteins, predominantly made of equal parts of glutenins and gliadins, which are resistant to digestion, and their partially digested epitopes are immunogenic and central to the process that leads to coeliac disease,3 4 an autoimmune condition characterised by an aberrant immune response to ingested gluten in genetically susceptible individuals, which results in small bowel inflammation, enteropathy and potential malabsorption.5 The prevalence of coeliac disease in the past 50 years has risen to approximately 0.7%–2%, a phenomenon attributed to increased awareness and detection, as well as a true increase in prevalence.6 7 The sole and current only curative treatment, a lifelong gluten-free diet, considered central to the management of coeliac disease has also seen increasing popularity in the general population; there is a widespread underlying belief that a gluten-free diet may be ‘healthier’, despite a lack of evidence to support this notion and even evidence that it may be harmful to the non-coeliac population.8 This has seen the gluten-free food industry boom to an estimated US$6 billion per year industry.5 Gluten, or more generally wheat, has also been associated with other GI disease. In the absence of coeliac disease and under the guise of the increasingly fashionable but controversial label ‘non-coeliac gluten/wheat sensitivity’ (NCG/WS), gluten has been popularised in the press as a potential cause of almost all possible conceivable physiological complaints, ranging from GI to neurological, dermatological, psychological and musculoskeletal …